The objective of the proposed research is to induce sublethal lesions in the sympathetic ganglia, adrenal medulla, substantia nigra, and neostriatum of the fetal rabbit by procedures that interfere with catecholamine metabolism. The lesions will be analyzed by fluorescence and electron microscopy. We will administer the following substances to the fetus or to the pregnant dam; L-dopa, alpha-methyl-p-tyrosine, reserpine, chlorpromazine, bretylium tosylate, guanethidine, or 6- hydroxydopamine. In addition, we will attempt to affect the development of catecholaminergic neuroblasts in the fetus by inducing hypoxia in the pregnant dam. The treatments enumerated may be expected to produce either minor alterations or extensive degeneration of a group of neurons depending on the procedure used and the stage of neuronal differentiation during which the treatment is initiated. After procedures have been developed which produce consistent lesions in viable fetuses, they will be carried to term and reared in the postnatal period. If these animals exhibit neurological signs resembling diseases which affect catecholaminergic neurons in man, we will have an animal model for testing various pharmacological agents which may reverse the deficit. Our electron microscopic investigations on normal development of neuroblasts, glia, and vasculature in the substantia nigra, neostriatum, and sympathetic nervous system will continue, since this information will be needed as a baseline for evaluating possible changes induced by the drug treatments and hypoxia experiments.